Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Hematalogy Lecture > Unit 3: Myeloproliferative Disorders > Flashcards

Unit 3: Myeloproliferative Disorders Flashcards

1
Q

MPNs =

A

monoclonal hyperproliferation abnormalities
(neoplasms) or myeloproliferative neoplasms.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

MPNs aka…

A

chronic non-lymphoid “malignancies”.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

MPNs usually affects what precursors?

A

erythroid, granulocyte, monocyte, or megakaryocyte precursors

-All can vary dramatically in presentation.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

MPNs:

All present as stable ___________ disorders, which can have ______ phases.

A

chronic, acute

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Can more than one MPN coexist?

A

-All can coexist with each other. (You can have > 1 at the same time!)
-All can transform into each other.
-All can transform into AML (& very rarely, even into ALL)!

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

MPN can exhibit hyper___________ and or hyper___________.

A

hypereosinophilia or hyperbasophilia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Ture or false:

MPN can have problems with thrombosis or hemorrhage.

A

True

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Why have MPNs been hard to classify?

A

due to overlapping characteristics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

MPNs are ________ in origin from a single pluripotential
hemopoietic stem cell.

A

Clonal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Major defect with Polycythemia Vera (PV)?

A

overproduction of RBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Major defect with Chronic Myelocytic Leukemia (CML)?

A

overproduction of granulocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Major defect with Essential Thrombocytosis (ET)?

A

overproduction of platelets

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Major defect with Myelofibrosis (PMF)?

A

overproduction of bone marrow fibroblasts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Etiology of Polycythemia Vera (PV)?

A

Clonal stem cell disorder (various mutations)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Causes unregulated proliferation of bone marrow erythroid, granulocytic, and megakaryocytic elements with ever-increasing RBC #s in p.b.

A

Polycythemia Vera (PV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

How to cells appear and function with Polycythemia Vera?

A

-all cells appear normal
-RBCs function normally, have N. lifespan.
-RBCs are normo- normo-….until Fe stores get used up.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Polycythemia Vera:

Best know mutation is in gene for protein called ____
(>90% of patients).

A

JAK2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

JAK2 is a…

A

nonreceptor tyrosine kinase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

It plays an important role for the EPO & TPO receptors up to their place on the RBC’s surface, so these cells are super sensitive!

A

JAK2 protein

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Even though hyperactivity of JAK2 may not initiate PV, it is…

A

associated with PV.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Stem cells with JAK2 mutation are resistant to…

A

erythropoietin apoptosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

_____ mutation also associated with ET & CIMF.

A

JAK2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

What are the two major criteria that both need to be met for Diagnosis of PV?

A
  1. Hgb level of:
    >18.5 g/dL in men
    >16.5 g/dL in women
  2. Identification of JAK2 mutation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

What are the 3 minor criterion for PV diagnosis? (only one needs to to be met along with the two major)

A
  1. panmyelosis in bone marrow
  2. low serum EPO level*
  3. autonomous, erythoid colony formation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

What are the clinical symptoms of PV?

A

 “Ruddy” face
 Itchy skin
 Hypertension
 Vertigo
 Feeling of fullness after eating only small amounts
 Blurred vision
 Headaches
 ↑ [uric acid]
 Splenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

PV symptoms:

LAP is…

A

increased

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

PV symptoms:

serum B12?
oxygen saturation?

A

increased

normal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Clinical Symptoms of PV:

Why a ruddy face?

A

Severely ↑ RBCS show up as pink color under the skin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Clinical Symptoms of PV:

Why hypertension?

A

Severely ↑ RBCS cause “sludgy” blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Clinical Symptoms of PV:

Why a feeling of fullness?

A

Splenomegaly pressure on stomach (from ↑ cell turnover)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Clinical Symptoms of PV:

Why increased uric acid?

A

↑ DNA degradation due to ↑ cell turnover

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

*** PV:

____ EPO levels

A

low

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

In all polycythemias: Absolute erythrocytosis, with:

RBC(T) =

A

6 - 10 x 10 6/uL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

PV:

Hgb >

A

18 g/dL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

PV:

Hct =

A

55 - 60%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

PV:

ESR =

A

0 - 3 mm/hr

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

PV:

_________ WBCs and plts., with N. morphology

A

Normal or increased

-Immature granulocytes and nRBCs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Platelet range seen with Polycythemia Vera?

A

400,000 - 2,000,000/uL

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

PV:

plts with _____ forms and ___________ function.

A

giant, abnormal

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

PV:

Bone marrow is __________, with worsening fibrosis

A

hypercellular

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

PV:

What decreases when disease progresses from “stable phase” to “spent phase”?

A

Fe stores

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

What is the treatment for Polycythemia Vera?

A

 No cure
 Therapeutic phlebotomy 1st choice
 Myelosuppressive drugs (Ex., hydroxyurea) can
↓ blood volume & ↑ Fe stores.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

What is the risk of Myelosuppressive drug treatment with Polycythemia Vera?

A

later risk of transformation into AML. (About 15% all PV pts. progress into AML eventually, anyway)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Clonal stem cell disorder
 Causes extreme elevation of both mature & immature myeloid cells in bone marrow.. which then shows up in the p.b.
 Slow clinical course
 Primarily seen in adults, but can occur at any age

A

Chronic Myelocytic / Myelogenous / Myeloid Leukemia (CML)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

CML clinical symptoms?

A

 Anemia
 Fever
 Excessive bleeding or bruising
 Malaise
 Hepatosplenomegaly

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Hepatosplenomegaly causes what to happen to the patient?

A

A feeling of fullness and eventual weight loss

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

CML:

> 95% pts. are ____________ chromosome +

A

Philadelphia (Ph’) ***

(unequal but reciprocal translocation of chromosomes 9 and 22)

48
Q

What is the prognosis for CML Ph’ pts.?

A

Good prognosis

49
Q

This translocation puts the c-ABL oncogene next to the
BCR (Breakpoint Cluster Region) gene. (There also can be additional large deletions on either side of this breakpoint.)

A

t (9,22), Philadelphia (Ph’) chromosome

50
Q

t (9,22) happens in what cells?

A

Translocation occurs in granulocytes, RBCs, mega-
karyocytes & lymphs.

51
Q

CML with t (9,22):

This translocation puts the c-ABL oncogene next to the
BCR (Breakpoint Cluster Region) gene. (There also can be additional large deletions on either side of this breakpoint.)

The product is a ____________ protein, enhances tyrosine kinase activity – 98% of pts. are
BCR / ABL +

A

BCR/ABL fusion***

– 98% of pts. are BCR / ABL +

52
Q

Why do cells with the t (9,22) defect accumulate even more defects?

A

Cells with this defect are hyperproliferative, AND
genetically unstable

53
Q

Ph’ and BCR/ABL protein can be diagnosed by…

A

-karyotyping (chromosomal level)
-FISH (cellular level)
-PCR (molecular level)

54
Q

What gene deletion can also occur in CML? What is the prognosis?

A

9q34 deletion in the argininosuccinate
synthetase gene

bad prognosis

55
Q

CML is “When the p.b. looks like…

A

bone marrow***

56
Q

THE HIGHEST WBC COUNTS IN ALL LEUKEMIAS COME
FROM _______!

A

CML***

57
Q

CML:

WBCT >___________/uL, & usually _____________/uL (!) with neutrophilia, basophilia, eosinophilia and often thrombocytosis.

A

100,000

200,000 - 500,000/

58
Q

CML shows a huge ______ shift with what developmental stages?***

A

left

all developmental stages

59
Q

CML:

~ ___ % blasts & pros, ____% myelos, _____ % metas,
_____% segs

A

1-5
10-20
10-30
30-50

*Both basophilia & eosinophilia can be seen

60
Q

CML:

> ___% basophilia heralds an impending blast crisis.

A

20*

61
Q

CML:

LAP score is ________ in early stages.

A

decreased

(but N. or increased in all other MPNs.)

62
Q

Plt. count with CML

A

often increased

-Pseudo-Pelger-Huet may be seen

63
Q

CML:

Anemia, if present, is morphologically typically
…

A

normo-, normo-

64
Q

What is the normal M:E ratio range in adults?

A

1.5:1 to 3.3:1

65
Q

CML:

Bone marrow shows striking increase in M:E ratio (can range from _________, but with ____ % blasts.)

A

10:1 - 50:1

<30

66
Q

Three phases of CML?

A

-chronic phase
-accelerated phase
-Blastic phase

67
Q

Three phases of CML:

 Usually occurs prior to blastic phase
 Poor response to therapies
 Increase in symptoms and lab values

A

accelerated phase

68
Q

Three phases of CML:

 Increased blast count to >20%
 Becomes either AML, or more rarely, ALL.

A

Blastic phase

69
Q

Previously the only cure for CML was BMT (performed while in chronic phase) now, what is the treatment?

A

Gleevec (imatinib mesylate) from Novartis Pharmaceuticals

70
Q

About _____ CML pts. undergo “blast transformation” from chronic into acute phase.

A

¾

71
Q

How does Gleevec work?

A

binds directly to the
BCR/ABL fusion
protein/tyrosine kinase produced by Ph’.
 Decreasing # of GF receptors in the abnormal cells, Gleevec causes abnormal cells to die
 As abnormal cells die, normal cells proliferate.

-And eventually no more abnormal, Ph translocation-
containing cells can be found = molecular remission

72
Q

What is the “cure” rate of CML with Gleevec?

A

> 88% of pts. in chronic phase (with variable
results in other phases).

73
Q

CML Treatment with Gleevec:

With effective therapy, the advent of monitoring for
_________________
has now become an important prognostic indicator.

A

Minimal Residual Disease*

74
Q

In general poorer CML prognoses are associated with increased…

A

 ↑ WBCT (> 100,000/uL)
 ↑ basophilia
 ↑ blasts
-Presence of any other abnormal cytogenetics.

75
Q

In general poorer CML prognosis with plt. counts that are…

A

very increased or very decreased (> 700,000/uL or
< 150,000/uL)

76
Q

NOTE: Ph’ neg. CML is now considered to be _______.

A

CMML

77
Q

Primary Myelofibrosis (PMF) aka…

A

Chronic Idiopathic Myelofibrosis (CIMF) and
Myelofibrosis with Myeloid Metaplasia, MMM!

78
Q

Primary Myelofibrosis (PMF) is a clonal stem cell disorder (associated with _____
mutation – 65% of patients)

A

JAK2

79
Q

Hyperproliferation of bone marrow fibroblasts (in response to neoplastic mutation elsewhere, that has caused the overproduction of GFs.)

A

Primary Myelofibrosis (PMF)

80
Q

Primary Myelofibrosis (PMF) can convert into _____!

A

AML

81
Q

Causes progressive bone marrow fibrosis (↑ collagen)
 Produces extensive extramedullary hematopoiesis with massive hepatosplenomegaly

A

Primary Myelofibrosis (PMF)

82
Q

Does Primary Myelofibrosis (PMF) cause splenomegaly?

A

massive hepatosplenomegaly!

83
Q

Myelofibrosis Clinical Symptoms

A

 Severe hepatosplenomegaly
 Abdominal pain
 Weight loss
 Normo-, normo cells
-normal symptoms of anemia

84
Q

Myelofibrosis is normo- normo anemia of normally sized & normally colored
RBCs, even though they may be…

A

teardrop-shaped, due
to the extramedullary hematopoiesis.

85
Q

What are the usual symptoms of anemia?

A

Pallor, malaise, & dyspnea

86
Q

Myelofibrosis Lab Findings:

 Highly variable!
 Characteristic: striking p.b. aniso/poik with teardrops/dacrocytes; why?***

A

Due to severe extra-
medullary hematopoiesis

87
Q

Myelofibrosis Lab Findings:

Poik becomes more severe as disease progresses to…

A

bone marrow failure!***

88
Q

Myelofibrosis Lab Findings:

______ shift & variably increased WBC count (_____________ uL, & doesn’t decrease with disease progression)

A

Left

15,000 - 30,000/

89
Q

Myelofibrosis Lab Findings:

Characteristic - _______ due to varying degrees of bone marrow fibrosis.

A

dry tap

90
Q

What three conditions characteristically have a dry tap?***

A

-PMF
-AMegL
-HCL

91
Q

Myelofibrosis have _________ plt. counts.

A

variable

92
Q

Myelofibrosis Treatment

A

 Chemo.
 Steroids
 Splenectomy
 Eventual bone marrow transplant

93
Q

Myelofibrosis:

What are the two most common complications of total bone marrow failure that patients die from?

A

overwhelming infections & massive hemorrhage

94
Q

Essential Thrombocythemia
(ET):

Clonal stem cell disorder (associated with ______ mutation)

A

JAK2

95
Q

Essential Thrombocythemia
(ET):

causes extremley increased _______ count

A

plt.

96
Q

Essential Thrombocythemia
(ET):

Plt. function is abnormal unless #s ↓ by
plateletpheresis – this differentiates it from what leukemia?

A

AML M7 - AMegL

97
Q

ET Clinical Symptoms

A

Abdominal pain
Epistaxis
GI bleeding
AND:
Bleeding after minor dental surgery
Thrombotic events

98
Q

What is the platelet count around with ET?

A

~ 600,000 -2,500,000/uL.

99
Q

What kind of plts. are found with ET?

A

Giant, bizarre plts., but NOT
megakaryocyte fragments in p.b.

100
Q

ET Lab Findings:

WBC findings?
plt. aggregation studies?

A

 Slt. leukocytosis with neutrophilia
 Abnormal plt. aggregation studies

101
Q

Note: M7/Acute megakaryoblastic leukemia (AMKL) has ______ in p.b.
ET is NOT usually accompanied by ____ _.

A

nRBCs

102
Q

Which is positive for giant plts.?

M7/Acute megakaryoblastic leukemia (AMKL) or ET?

A

Both

103
Q

Left shift:

M7/Acute megakaryoblastic leukemia (AMKL)?

ET?

A

M7 = rare left shift

ET = slight left shift

104
Q

megakaryocyte fragments:

M7/Acute megakaryoblastic leukemia (AMKL)?

ET?

A

M7 = positive

ET = no fragments

104
Q

ET Treatment

A

 Myelosuppressive drugs (Ex., hydroxyurea.)
 IFN-α if myelosuppressives can’t be given
 Plateletpheresis to reduce plt. mass
-Also restores normal plt function (for a while!)

105
Q

What is the risk of treating ET with Myelosuppressive drugs (Ex., hydroxyurea.) ?

A

Incurs higher risk of transforming into AML later on.

106
Q

The WHO breaks CML further into…

A

-Ph. chrom. - subtype
 CNL (Chronic Neutrophilic Leukemia, has no metas or myelos)
 CEL (Chronic Eosinophilic Leukemia)
 MPN, Unclassified

107
Q

WBC is typically _________x 10^3 uL with CML

A

> 100

108
Q

Hgb (g/dL) is ___________ with PV.

A

greatly increased

109
Q

Platelet count is _________ (x 10^3/uL) with PV.

A

> 1000

110
Q

Bone marrow fibroblasts are ___________ with PMF.

A

moderately increased to marked increase

111
Q

What is LAP score with early CML?

A

moderately decreased

112
Q

What is Lap score with PV?

A

Increased

113
Q

What is LAP score with PMF?

A

normal to increased

114
Q

What is LAP score with ET?

A

normal to increased

115
Q

Which Chronic Myeloproliferative disorder is associated with >95% Ph’ positive?

Which are negative?

A

CML

Negative for PV, PMF, and ET

Hematalogy Lecture (35 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions